Method for manufacturing a biological fluid sensor

ABSTRACT

The present invention presents a method of fabrication for a physiological sensor with electronic, electrochemical and chemical components. The fabrication method comprises steps for manufacturing an apparatus comprising at least one electrochemical sensor, a microcontroller, and a transceiver. The physiological sensor is operable to analyze biological fluids such as sweat.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.15/019,006, filed Feb. 9, 2016, which claims priority from U.S.Provisional Patent Application No. 62/130,047, filed Mar. 9, 2015, eachof which is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is generally directed to a method formanufacturing a device operable for collecting and analyzing biologicalfluid inputs, calculating biological fluid concentrations and ratios,and transmitting biological fluid values to a transceiver device.

2. Description of the Prior Art

Generally, biomarkers from biological fluid have significant prognosticand/or diagnostic utility, such as predicting disease, nutritionalimbalance, or psychological or physical stress; however, many of themost utilized biomarkers are collected from blood. The ability topredict events through non-invasive means, such as sweat detection,provides great utility to persons under physical stress, particularlyindividuals in the process of physical activity or exercise. The abilityto monitor sweat biomarkers real time and continuously during activityallows an individual to make informed decisions regarding hydration,nutrition, and exertional status, and recovery, all variables thatmoderate physical performance.

For example, hydration status is a predictor of physical performance;dehydration as low as 1% of body mass can impair performance. Prior artdetection and treatment, as shown in FIG. 1, is currently at the stagesof when symptoms present, performance degrades, and/or injury presents.Determining hydration through sweat biomarkers before dehydrationsymptoms present has many benefits, such as reducing fatigue, cramps,and headaches. Therefore, developing a device and system fornon-invasively obtaining biomarkers, such as through sweat, is needed.

Sweat contains a multitude of biomarkers; any substance aqueouslydissolvable in the blood can present in the sweat by way of eccrineglands. The sweat biomarkers can be small molecules, proteins,metabolites, and/or electrolytes. Well-known electrolytes in sweat aresodium and potassium. As shown in FIG. 2, potassium concentration is notdependent upon sweat rate due to the passive diffusive transport ofpotassium, while sodium and chloride concentrations in sweat aredependent upon sweat rate due to the active transport of sodium. Thus,monitoring sodium or chloride concentrations is an accurate, indirectmeans of indicating hydration status of an individual. Therefore,developing a sweat biomarker device that can communicate to anindividual real-time biomarker data is needed.

U.S. Pat. No. 6,198,953 for method and system for continuous sweatcollection and analysis by Webster, et al. filed Mar. 11, 1999 andissued Mar. 6, 2001 is directed to a method and system of the inventionprovide especially for continuously obtaining and analyzing, on a realtime basis, sweat from a selected area of skin on the body of a person,especially a neonate, being diagnosed for cystic fibrosis, by causingsweating of the selected area of skin, by placing an electricallypositive iontophoretic electrode device of a set of said devices overthe selected area of skin preferably within a previously placedreceiving and holding device which, following the induction of sweat andremoval of the electrically positive iontophoretic electrode device,receives a sweat-sensing electrode device that continuously sendselectrical signals to sweat analysis circuitry for providing a digitalreadout of the ionic composition of the sweat.

U.S. Pat. No. 8,388,534 for an apparatus providing skin care informationby measuring skin moisture content by Jang, et al. filed Sep. 24, 2007and issued Mar. 5, 2013 is directed to an apparatus for providing skincare information, the apparatus including: an electrode unit supplying avoltage to a user's skin and detecting a current signal in the user'sskin; a measurement control unit measuring the user's skin moisturecontent and sweat gland activity by using the detected current signal; adata calculation unit deriving skin moisture content information byusing the skin moisture content and the sweat gland activity, andgenerating skin care information corresponding to the skin moisturecontent information; and an information provider providing the user withthe generated skin care information is provided.

U.S. Pat. No. 7,575,549 for an apparatus and method for increasing,monitoring, measuring, and controlling perspiratory water and solid lossat reduced ambient pressure by Miller filed Jul. 30, 2004 and issuedAug. 18, 2009 is directed to a device for increasing, monitoring, andmeasuring perspiration water and solid loss at reduced ambient pressure,comprising a sealed chamber capable of maintaining less than atmosphericpressure for an extended period of time and a gasket-sealed dooraccessing the chamber. An algorithm allowing for continuous calculationsof sweat loss and fluid replacement requirements of the occupant of thechamber is disclosed.

US patent application 2014/330,096 for performing a physiologicalanalysis with increased reliability by Brunswick filed Nov. 12, 2012 andissued Nov. 6, 2014 is directed to a method for performing anelectrophysiological analysis implemented in a system includes: a seriesof electrodes to be placed on different regions of the human body; a DCvoltage source controlled so as to produce DC voltage pulses; aswitching circuit for selectively connecting the active electrodes tothe voltage source, the active electrodes forming an anode and acathode, and for connecting at least one other high-impedance passiveelectrode used to measure the potential reached by the body; and ameasuring circuit for reading data representative of the current in theactive electrodes, and data representative of the potentials generatedon at least certain high-impedance electrodes in response to theapplication of the pulses, the data allowing a value to be determinedfor the electrochemical conductance of the skin.

US patent application 2014/350,432 for assessment of relativeproportions of adrenergic and cholinergic nervous receptors withnon-invasive tests by Khalfallah and Brunswick filed Aug. 8, 2014 andissued Nov. 27, 2014 is directed to a system and method for assessingrelative proportions of cholinergic and adrenergic nervous receptors ina patient is disclosed. The system includes: an anode, a cathode, andpassive electrode for placement on different regions of the patientbody. The method generally includes: applying DC voltage pulses ofvarying voltage values to stress sweat glands of the patient, collectingdata representing the current between the anode and the cathode and thepotential of the anode, the cathode, and the passive electrode for eachof the different DC voltage, and computing data representing theelectrochemical skin conductance of the patient. The computed datarepresenting the electromechanical skin conductance of the patient isreconciled with reference data from control patients having knownrelative proportions of cholinergic and adrenergic nervous receptors.Thus, the relative proportions of cholinergic and adrenergic nervousreceptors in the patient can be determined.

US patent application 2015/019,135 for motion sensor and analysis byKacyvensky, et al. filed Jun. 3, 2014 and issued Jan. 15, 2015 isdirected to the performance of an individual being monitored based onmeasurements of a conformal sensor device. An example system includes acommunication module to receive data indicative of a measurement of atleast one sensor component of the conformal sensor device. The sensorcomponent obtains measurement of acceleration data representative of anacceleration proximate to the portion of the individual. A comparison ofa parameter computed based on the sensor component measurement to apreset performance threshold value provides an indication of theperformance of the individual.

The article Implementation of a Microfluidic Conductivity Sensor—APotential Sweat Electrolyte Sensing System for Dehydration Detection, byLiu, et al. in Conf Proc IEEE Eng Med Biol Soc, 2014:1678-81, discussesthe implementation of a microfluidic conductivity sensor—a potentialsweat electrolyte sensing system for dehydration detection.

Although biomarkers in sweat are appreciated, specifically electrolytesand glucose, a system and method is still lacking that continuouslyanalyzes sweat biomarkers in real time and transmits data to a user,which informs the user of his or her health status.

SUMMARY OF THE INVENTION

The present invention provides a method of fabrication for a biologicalfluid sensor with electronic, electrochemical and chemical components.

The fabrication method comprises steps for manufacturing an apparatuscomprising at least one electrochemical sensor, a microcontroller, and atransceiver. The fabrication process includes the steps of substratefabrication, circuit fabrication, pick and place, reflow soldering,electrode fabrication, membrane fabrication, sealing and curing, layerbonding, and dressing.

The present invention further includes a metallization paste andsequence step for a reference probe; and a metallization application andsequence step for at least one active probe. The present inventionfurther includes method steps for creating a sensor with line and spacecharacteristics configured and designed for sensing and/or analysis ofsweat flow rate and electrolyte probes. The present invention furtherincludes a method for membrane fabrication with precision ionophoreapplication and curing, and includes a method for dressing fabricationwith laser cutting, bonding, and assembly steps for microfluidic anddressing fabrication.

These and other aspects of the present invention will become apparent tothose skilled in the art after a reading of the following description ofthe preferred embodiment when considered with the drawings, as theysupport the claimed invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a chart demonstrating biomarker types, changes in biomarkerlevels during progressive stages of injury, and physiologicalpresentations associated with each stage of injury.

FIG. 2 shows a chart relating sweat rate to concentration ofelectrolytes.

FIG. 3 shows the multiple layers and associated parts of the sensorapparatus and a top perspective view of the complete sensor apparatus.

FIG. 4 shows a perspective top view of a flexible electronic layer onthe bottom adhesive layer.

FIG. 5 shows a complete flexible electronic layer.

FIG. 6 shows a separated layer of electrochemical sensors.

FIG. 7 shows the electrochemical sensors.

FIG. 8 shows a top perspective view (top) and bottom perspective(bottom) view of a complete sensor apparatus.

FIG. 9 shows a diagram of the sweat path through the sensor apparatus.

FIG. 10 shows a diagram of the analytical process within the sensorapparatus.

FIG. 11A shows a table of various sweat characteristics including basicratio for sweat flow rate, body surface area calcs, and sweat loss &body mass loss calcs.

FIG. 11B shows a chart of concentration of ions vs. sweat rate.

FIG. 11C shows tables including work level, zone, SFR, mV ratio, NaLoss, K Loss, Typ Wt, sweating rate and sweat sodium concentration and achart of frequency vs. Na loss.

FIG. 11D shows a table of sweat stds for a typical user.

FIG. 12A shows a table of basic electrolyte concentration conversions.

FIG. 12B shows a table of ratiometric analysis used within the sensorapparatus.

FIG. 12C shows a table of basic mV ratios.

FIG. 13A shows thresholds for electrolyte concentrations.

FIG. 13B shows a table of user input at session start, input from phone,and input from sensor.

FIG. 14 shows a diagram of the sweat sensor subsystem.

FIG. 15 shows a diagram of components within the sweat sensor subsystem.

FIG. 16 shows a diagram of sweat sensor communications.

FIG. 17 shows a diagram of a NXP semiconductor used in an embodiment ofthe sensor apparatus.

FIG. 18 shows a diagram of the communication between a NXP semiconductorand a wireless device in an embodiment of the sensor apparatus.

FIG. 19 shows a diagram of a sweat microcircuit of the sensor apparatus.

FIG. 20 shows a diagram of the system architecture.

FIG. 21 shows a diagram of the controls within the user mobile app ofthe wireless remote transceiver.

FIG. 22 shows a diagram of the network connection between the usermobile app and the user web service.

FIG. 23 shows a diagram of the controls within the cloud database andlibrary, which are part of the user web service.

FIG. 24 shows an individual view of the user web front.

FIG. 25 shows a multi-user view of the user web front.

FIG. 26 shows a diagram of the controls within the present invention'swebsite.

FIG. 27 shows an image of a user data base on the remote computerserver.

FIG. 28 shows a diagram of the generic cloud architecture.

FIG. 29 shows a diagram of a cloud enterprise.

FIG. 30 shows a diagram of another embodiment of a cloud enterprise.

FIG. 31 shows a diagram of a system for epidemiological research.

FIG. 32 shows a diagram of a manufacturing process for the sensorapparatus.

FIG. 33 shows a schematic diagram illustrating general components of acloud-based computer system.

FIG. 34 shows a diagram of a suite of sensors in addition to a sweatsensor.

FIG. 35 shows a top perspective view of one embodiment of the sensorapparatus.

FIG. 36 shows a top perspective view of another embodiment of the sensorapparatus.

FIG. 37A shows a top perspective view of a sensor with a liquidionophore coating.

FIG. 37 B shows a side perspective view of a sensor with a liquidionophore coating.

FIG. 37 C shows another side perspective view of a sensor with a liquidionophore coating.

FIG. 38A shows a top perspective view of a sensor with a liquidionophore coating which was formed using a well approach.

FIG. 38B shows a side perspective view of a sensor with a liquidionophore coating which was formed using a well approach.

FIG. 38C shows another side perspective view of a sensor with a liquidionophore coating which was formed using a well approach.

FIG. 39A shows a top perspective view of a sensor with a liquidionophore coating which was formed using a surface tension dam approach.

FIG. 39B shows a side perspective view of a sensor with a liquidionophore coating which was formed using a surface tension dam approach.

FIG. 40 shows a battery latch mitigation capacitor placement.

FIG. 41 shows an RC configuration with ground reference.

FIG. 42 shows an RC configuration with differential measurement.

FIG. 43 shows an example of cap placement Vcc to Ground for supplyvoltage stability and/or noise immunity.

DETAILED DESCRIPTION

The present invention includes methods of fabrication or manufacturing abiological fluid sensor device with electronic, electrochemical andchemical components for sensing and collecting biological fluidbiomarkers, transmitting data to a transceiver device on a remotecomputing device for calculating biomarker data, and analyzing the data,and storing the data on the remote computing device or on a remotecomputer server.

The present invention provides methods of making the sensor apparatus ordevice for sensing sweat biomarkers that are operable and functional asdescribed herein. A preferred embodiment is surface mount technology; itmay provide better electrical performance compared to hand soldering; itallows use of smaller electrical components, denser layout, cheaperboards, and improved shock and vibration characteristics. Electricalcomponents include chips, resistors, transistors, and capacitors. Anautomated dispenser configuration for dispensing an ionophore ispreferably used to ensure a higher unit production rate when comparedwith the prior art. The automated dispenser provides for precise andrapid ionophore coating.

The sequence of the steps as well as the steps themselves is critical tothe operational use and accuracy of the sensor apparatus. It is criticalto initially install the surface mount parts and run through solderreflow before assembly of the sensor units. Subsequently, the heatsensitive parts to include the reference electrode, active electrodes,and ionophore coatings should be applied in that order. Following thelast ionophore coating, the entire flexcircuit layer needs a minimumabout 3 hour cure, which can be accelerated by UV and/or other rapidheating/drying processes. Following the cure period, the sensors can befinal-assembled with the medical top cover, microfluidic, anddouble-sided skin adhesive layers using an industrial grade epoxy.

In a preferred embodiment, a microcircuit is printed directly on theflexible substrate using bare die bonding. The microcircuit is attachedto the flexible substrate using any common bare die bonding process,such as eutectic, solder, adhesive, glass or silver-glass.

The fabrication process includes the steps of substrate fabrication,circuit fabrication, pick and place, reflow soldering, electrodefabrication where the earlier heat intensive processes through refloware completed prior to the heat sensitive processes associated withstarting with the build up and treatment of metalized traces on thesubstrate followed by membrane fabrication, sealing and curing, anddressing. In one embodiment, the substrate is a Kapton substrate.Without this process sequence, the electrodes build up unpredictablelevels of oxidation and other undesirable surface conditions whichnegatively affect the accuracy within a sensor, as well as amongmultiple sensors. In a similar manner, the heat intensive steps alsodegrade/melt the ionophore coating, a polymer not tolerant of elevatedtemperature. Repeated heating and cooling exposes the ionophore tochemical changes and also creates microscopic holes in the coating, bothwhich allow untargeted biomarker ions to penetrate the coating to reachthe electrode which generates potential strength not associated with thetarget biomarker, thus reducing the accuracy.

The present invention further includes a metallization paste made of astable metal (silver, gold, platinum, palladium) on top of the circuittrace metal (typically copper or gold) which is further stabilizedthrough chemical and/or thermal annealing treatments to construct areference probe; and a similar metallization application and sequencestep for at least one active probe. The present invention furtherincludes method steps for creating a sensor with line and spacecharacteristics configured and designed for sensing and/or analysis ofsweat flow rate and small protein probes.

The present invention further includes a method for membrane fabricationwith precision ionophore application and curing. Sensor functionalityand accuracy require precision placement with proper thickness of asmall amount of ionophore polymer on the active electrodes tofilter/prevent untargeted ions to reach the electrode. The amount isapproximately 2 microliters with a designated viscosity placed in aclean assembly environment to completely cover the exposed activeelectrode on the skin-facing side of the flexcircuit. The coating shallpreferably not exceed more than 0.5 mm from the edge of the electrode.The placement also preferably includes automated dispenser configurationand settings to ensure high speed or high rate manufacturing as well asmanufacturing consistency that minimizes manufacturing accuracyvariations.

The present invention still further includes a method for dressingfabrication with laser cutting, bonding, and assembly steps formicrofluidic and dressing fabrication. Following the designatedionophore cure time, the flexcircuits with integrated parts, sensorelectrodes are conformal sealed and cured. The sealed flex circuits areplaced on a large sheet of top cover medical textile with previouslylaser precut patterns and adhesive up. The sealed flexcircuits adhere tothe top cover via the cover's adhesive; they are mechanicallyprecision-placed and pressed into place with the exposed sensor headfacing up for permanent bonding using proprietary edge bonding patternsto allow for the proper flow/exit of sweat from the sensor heads out.Next, microfluidic units previously pre-cut to specification areinserted on top via the same mechanical precision placement equipment.And finally the mechanical placement equipment places a large sheet ofdouble sided adhesive which were previously precut by laser to the samesize and pattern as the top cover textile. The sheet and each of thelaser precut patterns are precisely positioned above the semi-assembledunits below and pressed into position for permanent bond. The individualunits are then mechanically separated (punched) from their host sheetsand collected in bins for automated packaging into individualizedbranded wrappers, and then inserted into branded boxes that are cratedand palletized for shipment. The wrapper, box, crate, and palletspecifications are specified by our distribution partners' pack out planand specified branding schema.

FIG. 3. illustrates a multi-layered apparatus or device that includes adouble-sided adhesive layer, a filter paper, a electronic layer, and awoven top adhesive. More specifically, the device is flexible andmulti-layered, wherein the layers comprise the following: amacrofluidic, double-sided adhesive layer; a electronic layer comprisingat least one electrochemical sensor, a microcontroller, and atransceiver antenna coil; a microfluidic management layer; and a vaporporous, top protective layer. The macrofluidic, double-sided adhesivelayer is intimately adhered to the skin. The electronic layer isintimately adhered to the microfluidic, double-sided adhesive layer, asshown in FIG. 4. The microfluidic management layer circumferentiallysurrounds the at least one electrochemical sensor of the electroniclayer. The vapor porous, top protective layer is placed on andcompletely covers the microfluidic management layer and electroniclayer. The vapor-porous, top protective layer is intimately adhered tothe macrofluidic, double-sided adhesive layer. The fully fabricatedsensor apparatus is shown in FIG. 8. Preferably, the length of theapparatus is approximately 76.1 mm. In one embodiment, the adhesive ofthe apparatus is Double Coated Polyester Nonwoven Tape (commerciallyavailable as 3M 9917 as of this writing). In another embodiment, theadhesive of the apparatus is Tan Tricot Knit Tape (commerciallyavailable as 3M 9917 as of this writing). The design of the microfluidiclayer improves flow control and decreases patch layer delaminationduring high sweat volume use cases.

FIG. 34 shows a diagram illustrating a suite of sensors in addition to asweat sensor, including a non-invasive penetration (NIP) sensor, anaudio sensor, a vitals sensor, an electro-optical/infrared sensor, anoxygen sensor, a breath sensor, and a sweat sensor. In one embodimentthe sensor includes at least two of the sensors in FIG. 34. In anotherembodiment, one of the suite of sensors is the only sensor utilized. Oneor more of the sensors is embedded in the skin in one embodiment of thepresent invention. An embedded sensor preferably mimics the compositionand behavior of cells. The electro-optical/infrared sensor may include afluorescent signal sensor. In one embodiment, a reader sends anexcitation light through the skin to the biosensor, which then emits afluorescent light proportional to the amount of biochemical measured.

FIG. 35 shows a top perspective view of one embodiment of the sensorapparatus. The flex circuit is substantially centrally located on thebandage material and adhesive. Wicking paper is utilized to move bodilyfluid, particularly sweat, through the sensor apparatus. The reverse “D”shaped hole is through the adhesive and the wicking paper. Alldimensions in FIG. 35 are in MM or VOS, as appropriate.

FIG. 36 shows a top perspective view of another embodiment of the sensorapparatus. The flex circuit is substantially centrally located on thebandage material and adhesive. Wicking paper is utilized to move bodilyfluid, particularly sweat, through the sensor apparatus. The reverse “D”shaped hole is through the adhesive and the wicking paper. Alldimensions in FIG. 36 are in MM or VOS, as appropriate.

The sensor apparatus is designed to allow sweat to flow through lasercut, macrofluidic pores in the skin adhesive layer, as shown in FIG. 9.Sweat then flows through a filter to the electronics layer, specificallythe electrochemical sensor unit, where biomarkers may contact theelectrodes of the electrochemical sensor unit. The sweat evaporatesthrough the woven textile protective top layer. The evaporation affordsimproved and continuous sweat flow into the sensor apparatus. Thiswicking ensures sweat sensing measures are consistently using new sweatsamples rather than static or diluted samples. In one embodiment, thewicking and sweat flow rates range from 0% to 5% of Total Body Loss/hr(instant equivalent sweat loss rate) or equivalent to 11.5 L/hr totalloss.

The present invention further includes a device with a small amount ofionophore polymer on the active electrodes to filter/prevent untargetedions to reach the electrode. Sensor functionality and accuracy requireprecision placement with proper thickness of a small amount of ionophorepolymer in one embodiment. The precision placement is conducted eithermanually or via automated equipment. The amount of ionophore polymer isapproximately 2 microliters with a designated viscosity placed in aclean assembly environment to completely cover the exposed activeelectrode on the skin-facing side of the flexcircuit. The coating shallpreferably not exceed more than 0.5 mm from the edge of the electrode.In one embodiment, the ionophore polymer is cured. In anotherembodiment, the curing takes place using heat and/or light to acceleratedrying without changing the ionophore selectivity characteristics.

In one embodiment, the sensor is calibrated. Preferably, a human usercalibrates the sensor using actual test results and feedback from thesensor. Advantageously, human user calibration or human useself-calibration (H-SCAL) provides for more accurate data when comparedwith calibration of sensors solely in the laboratory. Actual human testdata is compared to external sweat loss ground truth obtained fromhighly accurate scales. The external data is utilized to adjust severalfactors for a human user. Specifically, the adjustments provide forcorrection of a collection of diminutive and/or major error sources toimprove the overall accuracy of the system.

The sensor apparatus includes sweat sensor subsystem, as shown in FIG.15, which includes a microcontroller that receives multiple input data,which are input from multiple sources. A first source is biologicalfluid, preferably sweat, although alternative fluids may be used. Thesweat contains a variety of analytes, such as, by way of example and notlimitation, electrolytes, small molecules, proteins, and metabolites.Exemplary analytes include substances including sodium or potassium. Inone embodiment, the sensor apparatus is operable to sense sodium andchloride both in a dynamic range from about 0 mM to about 120 mM, withnormal ranges in humans being about 20 mM to about 100 mM. In anotherembodiment, the sensor apparatus is operable to sense potassium in adynamic range from about 0 mM to about 40 mM, with normal ranges inhumans being about 5 mM to about 20 mM. In one embodiment, the sensorhas a response time of about 60 seconds with about a 90% response. Otheranalytes include oxygen, glucose, ammonium, and interleukins. In oneembodiment, the sensor is operable to analyze the analytes at a pMlevel, preferably in the 1-10 pM range or even below 1 pM (the sub-pMlevel). These analytes are collected at the electrochemical sensor, asshown in FIG. 7, which houses reference (preferably standard) and activeelectrodes, wherein, by example and not limitation, the electrodes aresilver, zinc, copper, gold, platinum, rhodium, carbon or a combinationthereof. In one embodiment, the apparatus has an embedded dot-circleconfiguration for a reference electrode to improve stability throughless interference. Additionally, gold probes or electrodes are used inone embodiment to improve stability and reduce production costs. Theapparatus also includes a microprocessor, multiplexer (mux), ADC, andoptimized on board processing for real time, pre-transmission sensorsignal conditioning in another embodiment.

Unique human induced electromagnetic interference (H-EMI) sometimescause interference and produce inaccurate measurements from the sensorapparatus. Specifically, human induced anomalies affect flex circuitfunctionality, performance, and reliability. Variations in the locationof the sensor on the human body as well as human skin variations betweenpeople can cause unpredictable flex circuit behavior that is not readilyapparent in lab settings. Through testing on humans, various embodimentsand solutions to H-EMI have been developed. In one embodiment, hardwarecomponents are placed to mitigate the human use electromagneticinterference effects on flex circuits. Specifically, the placement ofcapacitors compensates for intermittent power variations. Additionally,strategically placed Kapton reinforcements (or other polyimidecomponents) further mitigate EMI disturbances resulting from human useelectromagnetic interference. Specifically, capacitors are utilized onpower/battery latching circuits to mitigate human motion artifactsimpacting measurement cycles. FIG. 40 shows a battery latch mitigationcapacitor placement. The values included in FIG. 40 are for purposes ofillustration by example and in no way limit the values which areutilized in the present invention.

Adjustments in firmware running on a microcontroller also offset EMI insome embodiments. In another embodiment, adjustments to filtering(preferably by adding specific RLC components) and noise suppressionoffset EMI. Improved measurement electronics input design and samplingmethods also mitigate H-EMI. In one embodiment, input design involvescomplex impedance related to the RLC (mostly R and C) components tocondition sensor inputs to overcome motion artifacts manifest from thehuman sensor interface and input buffering methods to reduce measurementelectronics impact on sensor measurements (Heisenberg Uncertainty). FIG.41 shows an RC configuration with ground reference. FIG. 42 shows an RCconfiguration with differential measurement. FIG. 43 shows an example ofcap placement Vcc to Ground for supply voltage stability and/or noiseimmunity. Firmware branching logic preferably differentiates betweenpower on cycle and motion induced power variations.

The present invention also includes sensor embodiments which areoperable under the most demanding physical environments, and inparticular, athletic use cases. Specifically, a durable sensor is neededfor these cases because of exposure to violent impact shock, speedchanges, motion intensity, exposure to water, etc. Strengthening theflex circuit and electronic layouts minimize use case impacts on thesensor. Additionally, advanced flex circuit protection minimizes impactsupon the sensor. Advanced flex circuit protection includes strategicflex circuit mix with rigid boards and/or application-specificintegrated circuit (ASIC) miniaturization. Advanced rubberized casingsand microfluidics based on crystal fiber technology are also utilized inone embodiment. Specifically, the present invention includes theaforementioned adjustments to the sensor head of the sensor apparatus.Sensor heads accommodate a variety of motion factors, including flex,stretch, sliding, and shock loading. In one embodiment, the presentinvention utilizes multiple sensor configurations to accommodateindividual sensor disruption and/or failure.

In one embodiment, the sensor head is detachable and reattachable. Thesensor head is attached via z-axis tape or hot bar soldering in oneembodiment. In another embodiment, there is a standardizedinterconnection. In yet another embodiment, the sensor head pinout isselectable from the multiplexer side. In one embodiment, uC and a RFantenna are integrated with fabric. In yet another embodiment, two partencryption is utilized. RFI and shielding as well as adding layers tothe board to provide additional ground planes and/or metallized fabricin dressing are also utilized.

Additionally, flexibility in most components of the sensor apparatus isnot desired. FR4 is utilized in a preferred embodiment. The sensor headis the only flexible portion of the sensor in one embodiment, as thesensor head requires flex and adhesion to the human. However, forembodiments in which flexibility is desired, a variety of flexiblesubstrates are utilized.

Another embodiment of the present invention includes adding a layer orrow of 0 ohm resistors on either side of the multiplexer. Additionally,buffer amps are utilized either before or after the multiplexer. In analternative embodiment, higher impedance ADC is utilized. Faultdetection and isolation is also used in the systems and methods of thepresent invention.

FIG. 37A shows a top perspective view of a sensor with a liquidionophore coating. A circuit board or other substrate 701 includes acopper trace or other conductive material/circuit element 703, anionophore or any material applied using a liquid deposition method 705,and copper or other conductive material 707. The ionophore 705preferably covers the copper or other conductive material 707.

FIG. 37 B shows a side perspective view of a sensor with a liquidionophore coating.

FIG. 37 C shows another side perspective view of a sensor with a liquidionophore coating.

One sensor head embodiment of the present invention includes aRing-Reference design. This design preferably solves issues with surfacetension management.

FIG. 39A shows a top perspective view of a sensor with a liquidionophore coating which was formed using a surface tension dam approachor Ring-Reference design. A circuit board or other substrate 701includes a copper trace or other conductive material/circuit element703, an ionophore or any material applied using a liquid depositionmethod 705, copper or other conductive material 707, and a soldermask,printed ink, or any other non-conductive material dissimilar to thecircuit board printed, deposited to, or otherwise adhered to the circuitboard prior to liquid deposition 709. The ionophore 705 preferablycovers the copper or other conductive material 707.

FIG. 39B shows a side perspective view of a sensor with a liquidionophore coating which was formed using a surface tension dam approachor Ring-Reference design.

In another embodiment, a surface tension management solution includes aprinted or screened non-conductive ring inside a ring electrode tocreate a surface tension discontinuity. A soldermask preferably is asurface tension discontinuity in the surface tension managementsolution. In another embodiment, printed ink is a surface tensiondiscontinuity in the surface tension management solution. Printed inkrefers to any printed, screened, or deposited non-conductive material.This surface tension discontinuity supports the uniform deposition ofliquid ionophores. In another embodiment, a well design is utilized forthe sensor head for ionophore and electrode isolation. Specifically, thewell design mitigates the stretch and/or sliding issues by increasingabrasion resistance.

FIG. 38A shows a top perspective view of a sensor with a liquidionophore coating which was formed using a well approach. A circuitboard or other substrate 701 includes a copper trace or other conductivematerial/circuit element 703, an ionophore or any material applied usinga liquid deposition method 705, and copper or other conductive material707. The ionophore 705 preferably covers the copper or other conductivematerial 707.

FIG. 38B shows a side perspective view of a sensor with a liquidionophore coating which was formed using a well approach.

FIG. 38C shows another side perspective view of a sensor with a liquidionophore coating which was formed using a well approach.

The Ring-Reference design or surface tension management solution and thewell design are used to manage ionophore deposition, specifically liquiddeposition on a surface. The liquid is preferably deposited on thesurface of a circuit board and then solidifies and/or hardens.

Other variations in inter-sensor spacing are also utilized in thepresent invention. Variations in inter-sensor spacing improve sensorperformance on a human-sensor interface. Specifically, closer spacingbetween sensors generally contributes to crosstalk and parasitics. Thelocation and proximity of a reference sensor can also prevent issues forchemical, electrical, and mechanical isolation. Both chemical andmechanical interactions can compromise measurements of adjacent sensors,especially when sensors are of dissimilar construction and/or electricalspecification. Preferably, the location of a chloride sensor relative toa sodium sensor and/or a potassium sensor is varied to increase abrasionresistance, which mitigates stretching and/or sliding issues.Preferably, the location of the chloride sensor is not proximal to thelocation of Na and K sensors to avoid chemical and mechanicalinteractions between the sensors.

The sensor also includes a galvanic skin response sensor in oneembodiment. A longer lead and/or additional ground plane under thebattery are preferably utilized to resolve complications resulting fromadding a galvanic skin response sensor and/or a chlorine sensor.

In yet another embodiment, utilizing alternative flex substrates andconductor construction provides increase abrasion resistance.Preferably, silver ink on polyester or a material similar to polyesteris utilized.

Preferably, the sensor of the present invention does not include ajumper or a Galvanic Skin Response (GSR). In one embodiment, FR4 isadded under molex or directly integrated into the BR/uC and RF antenna.

The apparatus is also optimized for efficient and successfultransmission during athletic usage. When the electrodes contact thesweat biomarkers a voltage is produced. Three electrodes per analyte areused to create an average voltage value, which is transmitted to themicrocontroller, wherein the microcontroller pre-processes and preparesthe sensor data to be communicated to the transceiver device viaBluetooth for providing near field communication in preferredembodiments. Alternatively, an RFID, NFC, or other proprietarycommunications chip may be provided. The NFC chip preferably has anincreased base signal amplitude for better processing and lowerresolution as well as better concentration confidence and resolution.Bluetooth is preferred due to its low energy, ubiquity, and low cost.Most any Bluetooth enabled device can pair with another Bluetooth devicewithin a given proximity, which affords more ubiquitous communicationbetween the microcontroller and a transceiver device. The dynamic andautomatic connections of Bluetooth allow for multiple microcontrollersto communicate with a single transceiver device, which, by way ofexample and not limitation, would provide for a team-based situation,wherein the sweat data of multiple athletes is communicated to a singlecoach or team database.

Another embodiment provides for utilizing NFC and/or onboard power forsystem control and operation, NFC and serial interfaces for datatransport, external range extenders, and system integration.

Preferably, the systems and methods of the present invention are sensoragnostic, meaning that the systems and methods work with a variety ofsensors. By way of example and not limitation, the systems and methodsof the present invention work with multiple sensor head configurations,including variations in sensor count, single reference electrodesensors, multiple reference electrode sensors, a variety of analyteconcentration, a variety of analyte sensitivity, a variety of inputimpedances, analog measurement conditioning, digital sampling, etc.Notably, variations in hardware and/or firmware designs provide for thesensor agnostic systems and methods of the present invention. Anexemplary hardware implementation of a configurable sensor interface formultiple pinout permutations and variable analog buffering/signalconditioning supports existing and future sensor designs. Exemplaryfirmware designs for sensitivity and noise mitigation include, but arenot limited to, variable input impedance, sampling intervals, settlingtime, and input switching designs. Additionally, addling a settlingdelay between readings also mitigates noise. One embodiment of asettling delay includes switching the multiplexer, waiting 10 mS, thentaking a reading. Another embodiment for noise mitigation includeslowering the gain on the analog digital converter (ADC), which raisesinput impedance, to produce higher voltage levels. Adding both asettling delay and a lower ADC gain together significantly mitigatenoise.

Utilizing non-adjacent channel switching on a multiplexer also reducesnoise in the form of crosstalk and/or ghosting. Specifically, firmwaremethods for sensor switching and measurement times include non-adjacentmultiplexer selection and sensor specific settling times from sensorselection to ADC sampling. Standard single chip multiplexers canexperience adjacent channel crosstalk or ‘ghosting’ from large impedancechanges that can manifest as noise or erroneous measurements. Firmwaresolutions to avoid direct adjacency in measurement selection can reducethese effects and improve measurement electronics performance. This isparticularly important in low signal environments.

Complex sensor selection methods can propagate transition noise into themeasurement electronics. The settling time constant for different sensortypes and variations due to sensor-human interactions can present widefluctuations that are hard to manage with filtering. Firmware controlledselection-to-measurement time delays can mitigate these effects. Thiscan be implemented on a per sensor type basis for systems withdissimilar sensor types. As an example, a ‘ring reference’ ISE has morelocalized/uniform human contact behavior across the active sensor andits associated reference. In contrast, a ‘single reference-multiplesensor’ ISE can have widely differing human contact behavior due to thedistributed physical placement of the single reference and the specificsensor heads.

The systems and methods of the present invention preferably enableend-to-end flow and processing using a patch, wherein the data iseventually transmitted to a device or to the cloud for data processingand analytics. The patch preferably includes electronics and firmware toproperly buffer, amplify, and manage timing required to optimize patchfunctions. The firmware is preferably modularized to enable engineers toset designated variables, filters, noise thresholds, and otherattributes needed to accommodate many different sensor types,modalities, sensitivities, and other characteristics.

The present invention also provides systems and methods for addressingfault detection and isolation, electromagnetic compatibility (EMC)detection, radiofrequency interference detection, mitigation and eventhandling, addition of encryption for data integrity, personallyidentifiable information (PII) protection, and communications security.

A second source of input data is the remote transceiver device. Bytwo-way communication, the transceiver device may transmit data to themicrocontroller of the apparatus, which is part of an inter-integratedcircuit, as shown in FIGS. 17 and 18. The data to be transmitted willhave been manually or automatically input in the transceiver device. Forexample and not limitation, as shown in FIG. 10, types of manually inputdata may include gender, fitness or conditioning level, age, andanthropomorphic data such as height and weight. The anthropomorphic datais preferably used to estimate user body surface area, which is acritical variable for accurately determining sweat loss and electrolyteloss. More preferably, estimates are a product of anthropomorphic data,gender, and age. Prior art assumes a body surface area of about 2 m² tocalculate sweat loss and electrolyte loss. Using anthropomorphicvariables, as in the present invention, consistently decreasescalculated error rate from between about 50 and about 70 percent to lessthan about 10 percent, preferably. The accuracy resulting from body massestimation revealed that persons with larger body mass, such as males,more readily adapt to physical exertion by sweating more quickly, alarger volume, and lower electrolyte concentration. Similarly, aphysically fit person with a small body mass, such as a female, adaptsto physical exertion by adjusting sweat flow rates and electrolytelevels. Although prior art has validly analyzed sodium, potassium, sweatrates, etc., it has failed to account for body surface area, mass andVO2 max, thus inflating calculated error rate. These data support thatsweat flow rates and electrolyte loss is strongly correlated with bodysize and surface area and conditioning level, which further supports theneed for proper estimation of body size, such as through anthropomorphicvariables.

Other types of manually input data include metabolic disorder, such asdiabetes. Since Type 1 diabetes is associated with reduced eccrine glandactivation and, thus, lower sweat rates, the present invention mayreveal user metabolic disorder. Further, automatically input data mayinclude user skin temperature, outdoor or indoor temperature and/orhumidity and altitude. This data is also input manually in anotherembodiment. Other automatically input data and/or manually input dataincludes exertion levels and/or body mass. The automatically input datamay be generated in the remote transceiver device by integratedapplications, such as GPS or weather. Together, the data transmitted tothe microcontroller from the remote transceiver device representmodifying variables. Preferably, microcontroller software and/orsoftware on the computing device is operable to compensate forvariations across the automatically and/or manually input data.

The microcontroller converts the voltage data from the biological fluidinto a concentration or ratio value of the biomarker using at least oneprogrammed algorithm. For example, as shown in FIG. 11A, if thealgorithm was converting the amount of sodium ions detected at thesensor into a sodium concentration, the algorithm would apply around0.242 mM per mV of sodium. For potassium conversion, the ratio would bearound 0.195 mM per mV of potassium. In one embodiment, sensor data areinputs into real time blood serum hydration, sodium concentration, andpotassium concentration using absorption and extraction models that usesensor data as starting points. These calculated values are theapparatus' output data. Types of output data include but are not limitedto concentrations, such as molarity, osmolarity, and osmolality, anddescriptive statistics, such as averages, ratios, and trends, all ofwhich may be categorized based on a sub-range within a largerphysiological range of the biomarker, as shown in FIG. 13A. Themodifying variables transmitted from the remote transceiver device maymodify the algorithm, which may adjust the output data.

The output data is then transmitted wirelessly, preferably, throughwireless communication by the transceiver antenna (including a coil) ofthe apparatus. Using a larger antenna in the present invention providedfor lower data loss and easier reads associated with a broad x-yplacement tolerance. The wireless transmission is provided by anysuitable wireless communication, wireless network communication,standards-based or non-standards-based, by way of example and notlimitation, radiofrequency, Bluetooth, zigbee, wi-fi, near fieldcommunication, or other similar commercially utilized standards. At theremote transceiver device, the output data can be viewed and assessed bythe one or multiple users.

The basic fabrication process, as shown in FIG. 32, includes thefollowing steps: substrate fabrication, circuit fabrication, pick andplace, reflow soldering, electrode fabrication, circuit boardprogramming, membrane fabrication, sealing and curing, and dressing.

Electrode fabrication includes the described novel metallization pasteand sequence for the reference probe; novel metallization applicationand sequence for active probes; novel line and space characteristics forsweat flow rate and small protein probes.

Membrane fabrication entails the described novel precision ionophoreapplication and cure processes.

Dressing entails the described novel laser cutting, bonding, andassembly steps for fabricating the microfluidic components and thedressing.

FIG. 33 is a schematic diagram of an embodiment of the inventionillustrating a cloud-based computer system, generally described as 800,having a network 810, a plurality of computing devices 820, 830, 840, aserver 850 and a database 870.

The server 850 is constructed, configured and coupled to enablecommunication over a network 810 with a computing devices 820, 830, 840.The server 850 includes a processing unit 851 with an operating system852. The operating system 852 enables the server 850 to communicatethrough network 810 with the remote, distributed user devices. Database870 may house an operating system 872, memory 874, and programs 876.

In one embodiment of the invention, the system 800 includes acloud-based network 810 for distributed communication via a wirelesscommunication antenna 812 and processing by a plurality of mobilecommunication computing devices 830. In another embodiment of theinvention, the system 800 is a virtualized computing system capable ofexecuting any or all aspects of software and/or application componentspresented herein on the computing devices 820, 830, 840. In certainaspects, the computer system 800 may be implemented using hardware or acombination of software and hardware, either in a dedicated computingdevice, or integrated into another entity, or distributed acrossmultiple entities or computing devices.

By way of example, and not limitation, the computing devices 820, 830,840 are intended to represent various forms of digital computers 820,840, 850 and mobile devices 830, such as a server, blade server,mainframe, mobile phone, a personal digital assistant (PDA), a smartphone, a desktop computer, a netbook computer, a tablet computer, aworkstation, a laptop, and other similar computing devices. Thecomponents shown here, their connections and relationships, and theirfunctions, are meant to be exemplary only, and are not meant to limitimplementations of the invention described and/or claimed in thisdocument

In one embodiment, the computing device 820 includes components such asa processor 860, a system memory 862 having a random access memory (RAM)864 and a read-only memory (ROM) 866, and a system bus 868 that couplesthe memory 862 to the processor 860. In another embodiment, thecomputing device 830 may additionally include components such as astorage device 890 for storing the operating system 892 and one or moreapplication programs 894, a network interface unit 896, and/or aninput/output controller 898. Each of the components may be coupled toeach other through at least one bus 868. The input/output controller 898may receive and process input from, or provide output to, a number ofother devices 899, including, but not limited to, alphanumeric inputdevices, mice, electronic styluses, display units, touch screens, signalgeneration devices (e.g., speakers) or printers.

By way of example, and not limitation, the processor 860 may be ageneral-purpose microprocessor (e.g., a central processing unit (CPU)),a graphics processing unit (GPU), a microcontroller, a Digital SignalProcessor (DSP), an Application Specific Integrated Circuit (ASIC), aField Programmable Gate Array (FPGA), a Programmable Logic Device (PLD),a controller, a state machine, gated or transistor logic, discretehardware components, or any other suitable entity or combinationsthereof that can perform calculations, process instructions forexecution, and/or other manipulations of information.

In another implementation, shown as 840 in FIG. 33, multiple processors860 and/or multiple buses 868 may be used, as appropriate, along withmultiple memories 862 of multiple types (e.g., a combination of a DSPand a microprocessor, a plurality of microprocessors, one or moremicroprocessors in conjunction with a DSP core).

Also, multiple computing devices may be connected, with each deviceproviding portions of the necessary operations (e.g., a server bank, agroup of blade servers, or a multi-processor system). Alternatively,some steps or methods may be performed by circuitry that is specific toa given function.

According to various embodiments, the computer system 800 may operate ina networked environment using logical connections to local and/or remotecomputing devices 820, 830, 840, 850 through a network 810. A computingdevice 830 may connect to a network 810 through a network interface unit896 connected to the bus 868. Computing devices may communicatecommunication media through wired networks, direct-wired connections orwirelessly such as acoustic, RF or infrared through an antenna 897 incommunication with the network antenna 812 and the network interfaceunit 896, which may include digital signal processing circuitry whennecessary. The network interface unit 896 may provide for communicationsunder various modes or protocols.

In one or more exemplary aspects, the instructions may be implemented inhardware, software, firmware, or any combinations thereof. A computerreadable medium may provide volatile or non-volatile storage for one ormore sets of instructions, such as operating systems, data structures,program modules, applications or other data embodying any one or more ofthe methodologies or functions described herein. The computer readablemedium may include the memory 862, the processor 860, and/or the storagemedia 890 and may be a single medium or multiple media (e.g., acentralized or distributed computer system) that store the one or moresets of instructions 900. Non-transitory computer readable mediaincludes all computer readable media, with the sole exception being atransitory, propagating signal per se. The instructions 900 may furtherbe transmitted or received over the network 810 via the networkinterface unit 896 as communication media, which may include a modulateddata signal such as a carrier wave or other transport mechanism andincludes any delivery media. The term “modulated data signal” means asignal that has one or more of its characteristics changed or set in amanner as to encode information in the signal.

Storage devices 890 and memory 862 include, but are not limited to,volatile and non-volatile media such as cache, RAM, ROM, EPROM, EEPROM,FLASH memory or other solid state memory technology, disks or discs(e.g., digital versatile disks (DVD), HD-DVD, BLU-RAY, compact disc(CD), CD-ROM, floppy disc) or other optical storage, magnetic cassettes,magnetic tape, magnetic disk storage or other magnetic storage devices,or any other medium that can be used to store the computer readableinstructions and which can be accessed by the computer system 800.

It is also contemplated that the computer system 800 may not include allof the components shown in FIG. 33, may include other components thatare not explicitly shown in FIG. 33, or may utilize an architecturecompletely different than that shown in FIG. 33. The variousillustrative logical blocks, modules, elements, circuits, and algorithmsdescribed in connection with the embodiments disclosed herein may beimplemented as electronic hardware, computer software, or combinationsof both. To clearly illustrate this interchangeability of hardware andsoftware, various illustrative components, blocks, modules, circuits,and steps have been described above generally in terms of theirfunctionality. Whether such functionality is implemented as hardware orsoftware depends upon the particular application and design constraintsimposed on the overall system. Skilled artisans may implement thedescribed functionality in varying ways for each particular application(e.g., arranged in a different order or partitioned in a different way),but such implementation decisions should not be interpreted as causing adeparture from the scope of the present invention.

By way of definition and description supporting the claimed subjectmatter, preferably, the present invention includes communicationmethodologies for transmitting data, data packets, messages or messagingvia a communication layer. Wireless communications over a network arepreferred. Correspondingly, and consistent with the communicationmethodologies for transmitting data or messaging according to thepresent invention, as used throughout this specification, figures andclaims, wireless communication is provided by any reasonable protocol orapproach, by way of example and not limitation, Bluetooth, Wi-Fi,cellular, zigbee, near field communication, or other similarcommercially utilized standards; the term “ZigBee” refers to anywireless communication protocol adopted by the Institute of Electronics& Electrical Engineers (IEEE) according to standard 802.15.4 or anysuccessor standard(s), the term “Wi-Fi” refers to any communicationprotocol adopted by the IEEE under standard 802.11 or any successorstandard(s), the term “WiMax” refers to any communication protocoladopted by the IEEE under standard 802.16 or any successor standard(s),and the term “Bluetooth” refers to any short-range communicationprotocol implementing IEEE standard 802.15.1 or any successorstandard(s). Additionally or alternatively to WiMax, othercommunications protocols may be used, including but not limited to a“1G” wireless protocol such as analog wireless transmission, firstgeneration standards based (IEEE, ITU or other recognized worldcommunications standard), a “2G” standards based protocol such as “EDGEor CDMA 2000 also known as 1×RTT”, a 3G based standard such as “HighSpeed Packet Access (HSPA) or Evolution for Data Only (EVDO), anyaccepted 4G standard such as “IEEE, ITU standards that include WiMax,Long Term Evolution “LTE” and its derivative standards, any Ethernetsolution wireless or wired, or any proprietary wireless or power linecarrier standards that communicate to a client device or anycontrollable device that sends and receives an IP based message. Theterm “High Speed Packet Data Access (HSPA)” refers to any communicationprotocol adopted by the International Telecommunication Union (ITU) oranother mobile telecommunications standards body referring to theevolution of the Global System for Mobile Communications (GSM) standardbeyond its third generation Universal Mobile Telecommunications System(UMTS) protocols. The term “Long Term Evolution (LTE)” refers to anycommunication protocol adopted by the ITU or another mobiletelecommunications standards body referring to the evolution ofGSM-based networks to voice, video and data standards anticipated to bereplacement protocols for HSPA. The term “Code Division Multiple Access(CDMA) Evolution Date-Optimized (EVDO) Revision A (CDMA EVDO Rev. A)”refers to the communication protocol adopted by the ITU under standardnumber TIA-856 Rev. A.

It will be appreciated that embodiments of the invention describedherein may be comprised of one or more conventional processors andunique stored program instructions that control the one or moreprocessors to implement, in conjunction with certain non-processorcircuits, some, most, or all of the functions for the systems andmethods as described herein. The non-processor circuits may include, butare not limited to, radio receivers, radio transmitters, antennas,modems, signal drivers, clock circuits, power source circuits, relays,current sensors, and user input devices. As such, these functions may beinterpreted as steps of a method to distribute information and controlsignals between devices. Alternatively, some or all functions could beimplemented by a state machine that has no stored program instructions,or in one or more application specific integrated circuits (ASICs), inwhich each function or some combinations of functions are implemented ascustom logic. Of course, a combination of the two approaches could beused. Thus, methods and means for these functions have been describedherein. Further, it is expected that one of ordinary skill in the art,notwithstanding possibly significant effort and many design choicesmotivated by, for example, available time, current technology, andeconomic considerations, when guided by the concepts and principlesdisclosed herein, will be readily capable of generating such softwareinstructions, programs and integrated circuits (ICs), and appropriatelyarranging and functionally integrating such non-processor circuits,without undue experimentation.

Certain modifications and improvements will occur to those skilled inthe art upon a reading of the foregoing description, by way of example,a device having at least one microprocessor for storing data may beoperable in the device before data transmission. Another exampleincludes other advanced sensors, as well as being incorporated intosmart fabrics and protective wear. Advanced sensors include advancedsweat biomarkers, pulse rate breath rate, micro EKG, micro O2, picturelog, voice log, voice translate, tissue safe X-ray and combinationsthereof. Smart fabrics incorporate the present invention and includeactive heat/cooling, kinetic energy generation, electromagnetic energyharvesting, wearable energy storage, wearable data storage, wearableprocessing, wearable communications, elastomeric actuators, andcombinations thereof. More generally, the apparatus may be part ofapparel and material for lower body clothing and upper body clothing.The present invention is also incorporated into enhanced protective wearsuch as enhanced helmets, gloves and footwear. Specifically, sensors,conductors and/or ionophores are utilized on moisture managementfabrics, such as by way of example and not limitation, Under Armourfabrics. Microfluidic moisture transport is also utilized in fabric andother material which directly contacts human skin when worn. Enhancedhelmets include those with MRI, 3D audio, visual enhancement, mixedreality, breath sensors, aerosol nutrition and combinations thereof.Enhanced gloves include touch communications, elastomeric grip, gesturecontrol and combinations thereof. Enhanced footwear includes powergeneration boots, 3D tracking, tactile alerts, communicationtransceivers, and combinations thereof.

The above mentioned examples are provided to serve the purpose ofclarifying the aspects of the invention and it will be apparent to oneskilled in the art that they do not serve to limit the scope of theinvention. All modifications and improvements have been deleted hereinfor the sake of conciseness and readability but are properly within thescope of the present invention.

What is claimed is:
 1. A method of fabrication for a physiologicalsensor for analyzing biological fluid from a human with electronic,electrochemical and chemical components, the method comprising:fabricating a substrate; fabricating a circuit; picking and placing theelectronic components onto the circuit; reflow soldering of the circuit;fabricating at least one electrode; fabricating a membrane; sealing andcuring the at least one electrode; and fabricating a dressing.
 2. Themethod of claim 1, wherein the physiological sensor comprises at leastone electrochemical sensor, a microcontroller, and a transceiver.
 3. Themethod of claim 2, wherein the at least one electrochemical sensorhouses the at least one electrode, wherein the at least one electrodeincludes a standard electrode and an active electrode.
 4. The method ofclaim 3, wherein the standard electrode and the active electrode includesilver, zinc, copper, gold, platinum, rhodium, carbon, and/or acombination thereof.
 5. The method of claim 2, wherein the physiologicalsensor is a biological fluid sensor operable to analyze a biologicalfluid.
 6. The method of claim 5, wherein the biological fluid is sweat.7. The method of claim 6, wherein the at least one electrochemicalsensor is operable to detect and continuously analyze at least onebiomarker of the sweat.
 8. The method of claim 7, wherein the at leastone biomarker of the sweat includes electrolytes, small molecules,proteins, and/or metabolites.
 9. A method of fabrication for abiological fluid sensor for analyzing biological fluid from a human withelectronic, electrochemical and chemical components, the methodcomprising: fabricating a substrate; fabricating a circuit; picking andplacing the electronic components onto the circuit; reflow soldering ofthe circuit; fabricating at least one electrode; fabricating a membrane;sealing and curing the at least one electrode; and fabricating adressing; wherein fabricating the at least one electrode furthercomprises: fabricating a metallization paste and sequencing a referenceprobe; applying the metallization paste to at least one active probe;sequencing the at least one active probe; and creating the biologicalfluid sensor with line and space characteristics, wherein the biologicalfluid sensor is operable to analyze a biological fluid.
 10. The methodof claim 9, wherein the biological fluid sensor comprises at least oneelectrochemical sensor, a microcontroller, and a transceiver.
 11. Themethod of claim 9, wherein the biological fluid is sweat.
 12. The methodof claim 11, wherein the biological fluid sensor is configured anddesigned for sensing and/or analyzing sweat flow rate and small proteinprobes.
 13. The method of claim 9, wherein the metallization paste ismade of at least one stable metal selected from the group consisting ofsilver, gold, platinum, and/or palladium.
 14. A method of fabricationfor a biological fluid sensor for analyzing biological fluid from ahuman with electronic, electrochemical and chemical components, themethod comprising: fabricating a substrate; fabricating a circuit;picking and placing the electronic components onto the circuit; reflowsoldering of the circuit; fabricating an electrode; fabricating amembrane; sealing and curing the electrode; and fabricating a dressing;wherein the step of fabricating the membrane further comprises applyingan ionophore polymer coating on the electrode and curing the ionophorepolymer coating; and wherein the step of fabricating the dressingfurther comprises: laser cutting; bonding; and assembling the electroniccomponents and the dressing, wherein the biological fluid sensor isoperable to analyze a biological fluid.
 15. The method of claim 14,wherein the biological fluid sensor comprises at least oneelectrochemical sensor, a microcontroller, and a transceiver.
 16. Themethod of claim 14, wherein applying the ionophore polymer coating onthe electrode is performed via an automated dispenser.
 17. The method ofclaim 15, wherein the at least one electrochemical sensor is operable todetect and continuously analyze at least one biomarker of the sweat. 18.The method of claim 17, wherein the at least one biomarker of the sweatincludes electrolytes, small molecules, proteins, and/or metabolites.19. The method of claim 14, wherein about 2 microliters of the ionophorepolymer coating is applied to the electrode.
 20. The method of claim 14,wherein the ionophore polymer coating does not exceed more than about0.5 millimeters from the edge of the electrode.